Our major goal is to test the effect of varying doses of dietary vitamin E on the tumorigenicity of established tumor cell lines. Inasmuch as the influence of vitamin E is often modified by the presence of polyunsaturated fatty acids (PUFA), the titration of vitamin E will be against a background of different levels of dietary PUFA. The impetus for this work has been our observation that it is possible to isolate a tumor cell varient whose tumorigenicity is relatively insensitive to changes in dietary fat compared with the original tumor cell line. This varient was isolated by growth in cell culture media which have been depleted in lipids. It was found that in mice fed a diet containing 4% lard, the original tumor cell line was least tumorigenic when moderate levels of vitamin E was included in the diet relative to that seen when high levels or no vitamin E were present. The varient was unaffected by these dietary alterations. Given these otherwise isogenic strains, it would appear that they offer an excellent model system to investigate the mode of action of fats and vitamin E on tumorigenicity. Since tumorigenicity can be affected by tumor growth rate and the host's defense mechanisms, it is our intention to study the effect of vitamin E in diets varing in PUFA levels on tumor growth, the host's immune response to tumors and the susceptibility of the tumor cells to these defense mechanisms. It is expected that this approach in an animal model will produce information useful to determining whether megadose levels of vitamin E or other lipid alterations in the diet can result in diminishing the incidence of cancer.